Factors Affecting Disease Stability After Intravitreal Brolucizumab Injection for Refractory Neovascular Age-Related Macular Degeneration.

INTRODUCTION: The purpose of this study is to identify the factors affecting neovascular age-related macular degeneration (nAMD) disease stability after brolucizumab treatment. METHODS: We retrospectively analyzed the medical records of 31 patients (31 eyes) with recalcitrant nAMD who were switched to brolucizumab after conventional anti-vascular endothelial growth factor (VEGF) treatment. We divided patients into two groups by treatment extension (TE) period: group 1 with TE < 12 weeks (N = 16) and group 2 with TE ≥ 12 weeks (N = 15). We compared outcomes between the groups at 2, 4, 8, and 12 weeks, including morphological characteristics of choroidal neovascularization (CNV). Logistic regression analysis identified factors associated with TE ≥ 12 weeks. RESULTS: Group 2 had a significantly greater proportion of patients with dry macula (subretinal and intraretinal fluids absent) than group 1 (60 vs. 12.5%) at 2 weeks (P < 0.05). Best-corrected visual acuity (BCVA) and subfoveal choroidal thickness (SFCT) did not differ significantly between groups at all timepoints. Central subfield retinal thickness (CST) was significantly lower in group 2 at 2 (237.1 vs. 280.8 µm; P < 0.05), 4 (224.0 vs. 262.9 µm; P < 0.05), and 8 weeks (216.8 vs. 331.1 µm; P < 0.05). Group 2 had less vessel area (0.63 vs. 1.27 mm2; P < 0.05) and total vessel length (0.22 vs. 0.42 mm; P < 0.05). Choriocapillaris flow deficit (CCFd) was significantly lower in group 2 (42.7 vs. 48.2%; P < 0.05). Dry macula at 2 weeks (odds ratio [OR] = 8.3; P < 0.05) and a lower CCFd (OR = 0.73; P < 0.05) were associated with TE ≥ 12 weeks. CONCLUSIONS: Early fluid-free status after switching to brolucizumab and choriocapillary function around CNV were prognostic factors for disease stability in nAMD refractory to anti-VEGF treatment.

Impact of treatment interval between neoadjuvant immunochemotherapy and surgery in lung squamous cell carcinoma.

OBJECTIVE: The optimal timing for surgery following neoadjuvant immunochemotherapy for lung squamous cell carcinoma appears to be a topic of limited data. Many clinical studies lack stringent guidelines regarding this timing. The objective of this study is to explore the effect of the interval between neoadjuvant immunochemotherapy and surgery on survival outcomes in patients with lung squamous cell carcinoma. METHODS: This study conducted a retrospective analysis of patients with lung squamous cell carcinoma who underwent neoadjuvant immunochemotherapy between January 2019 and October 2022 at The First Affiliated Hospital, Zhejiang University School of Medicine. Patients were divided into two groups based on the treatment interval: ≤33 days and > 33 days. The primary observational endpoints of the study were Disease-Free Survival (DFS) and Overall Survival (OS). Secondary observational endpoints included Objective response rate (ORR), Major Pathological Response (MPR), and Pathological Complete Remission (pCR). RESULTS: Using the Kaplan-Meier methods, the ≤ 33d group demonstrated a superior DFS curve compared to the > 33d group (p = 0.0015). The median DFS for the two groups was 952 days and 590 days, respectively. There was no statistical difference in the OS curves between the groups (p = 0.66), and the median OS was not reached for either group. The treatment interval did not influence the pathologic response of the tumor or lymph nodes. CONCLUSIONS: The study observed that shorter treatment intervals were associated with improved DFS, without influencing OS, pathologic response, or surgical safety. Patients should avoid having a prolonged treatment interval between neoadjuvant immunochemotherapy and surgery.

Delays in presentation, diagnosis, and treatment in Sudanese women with breast cancer: a cross-sectional study.

BACKGROUND: The poor prognosis of breast cancer in Sudan could be due to delayed treatment and diagnosis at an advanced stage. Our study aimed to assess the extent of delays from onset of symptoms to treatment in Sudanese women with breast cancer, as well as identify factors contributing to these delays. MATERIALS AND METHODS: We conducted a multi-center cross sectional study between March and April 2023. Data were collected from the medical records and interviews with women with breast cancer in the two main oncology centers in Sudan. Linear regression was used to identify the predictors of delayed presentation. RESULTS: We interviewed 601 women with breast cancer. The majority of women (50.1%) were diagnosed at locally advanced or metastatic disease. The median interval from the onset of symptoms to receiving oncologic treatment was 221 days (IQR = 92, 496). The longest delay was the presentation delay 61 (31 244) days. The median duration for diagnosis delay and treatment delay was 21 (10.57) days and 27 (10.64) days, respectively. Predictors of early presentation included, being young (ß = -5.3; 95% CI = 0.06 to 10), married (ß = -264; 95% CI = -427 to -101), divorced (ß = -306; 95% CI = -549 to -63), or widowed (ß = -320; 95% CI = --543 to -97), urban residence (ß = -107; 95% CI = -213 to -2.3), and seeking traditional healer (ß = -204; 95% CI = -383 to -26). CONCLUSION: Most Sudanese women with breast cancer experience significant patient delays, often presenting at advanced stages. Factors like being single, older, and living in rural areas contribute to these delays. Increasing breast cancer education, improving healthcare access and addressing sociodemographic barriers can potentially expedite diagnosis and improve outcomes.

Extended interval dosing with ocrelizumab in multiple sclerosis.

BACKGROUND: This study investigates clinical and biomarker differences between standard interval dosing (SID) and extended interval dosing (EID) of ocrelizumab therapy in multiple sclerosis (MS). METHODS: This is a prospective, double-arm, open-label, multi-center study in Denmark. Participants diagnosed with MS on ocrelizumab therapy >12 months were included (n = 184). Clinical, radiological, and blood-based biomarker outcomes were evaluated. MRI disease activity, relapses, worsening of neurostatus, and No Evidence of Disease Activity-3 (NEDA-3) were used as a combined endpoint. RESULTS: Out of 184 participants, 107 participants received EID (58.2%), whereas 77 participants received SID (41.8%). The average extension was 9 weeks with a maximum of 78 weeks. When comparing EID to SID, we found higher levels of B-cells, lower serum concentrations of ocrelizumab, and similar levels of age-adjusted NFL and GFAP in the two groups. No difference in NEDA-3 between EID and SID was demonstrated (hazard ratio: 1.174, p = 0.69). Higher levels of NFL were identified in participants with disease activity. Body mass index correlated with levels of ocrelizumab and B-cells. CONCLUSION: Extending one treatment interval of ocrelizumab on average 9 weeks and up to 78 weeks did not result in clinical, radiological, or biomarker evidence of worsening compared with SID.

Intravitreal Aflibercept for Neovascular Age-Related Macular Degeneration Beyond One Year of Treatment: AZURE, a Randomized Trial of Treat-and-Extend vs. Fixed Dosing.

INTRODUCTION: AZURE was a 76-week, randomized, open-label, parallel-group, phase IIIb noninferiority study comparing the efficacy and safety of intravitreal aflibercept (IVT-AFL) in a treat-and-extend (T&E) regimen with fixed dosing in patients with neovascular age-related macular degeneration (nAMD) previously receiving IVT-AFL for ≥ 1 year. METHODS: Patients were aged ≥ 51 years and had completed ≥ 1 year of IVT-AFL treatment prior to enrollment (IVT-AFL once per month [- 1 or + 2 weeks] for 3 months followed by IVT-AFL every 2 months [6-12 weeks]). Patients were randomly assigned (1:1) to receive IVT-AFL 2 mg in either a T&E (minimum treatment interval of 8 weeks with no upper limit, adjusted according to functional and anatomic outcomes, as assessed by the investigator; n = 168), or a fixed dosing regimen (treatment every 8 weeks [± 3 days]; n = 168). The primary endpoint was best-corrected visual acuity (BCVA) change from baseline to week (W) 52. The key secondary endpoint was the proportion of patients maintaining vision (< 15-letter loss) at W52. RESULTS: The full analysis set comprised 332 patients (T&E: n = 165; fixed dosing: n = 167). Mean BCVA change (baseline to W52) was - 0.3 ± 7.5 vs. - 0.5 ± 8.4 letters (T&E vs. fixed dosing; least-squares mean difference [95% CI]: 0.22 [- 1.51 to 1.96] letters; P < 0.0001 for noninferiority test [5-letter margin]). From baseline to W52, 95.2% (T&E) and 94.0% (fixed dosing) of patients maintained vision. Mean central subfield thickness change from baseline to W52 was - 24 ± 55 (T&E) and - 33 ± 47 (fixed dosing) µm. Last treatment interval to W76 was ≥ 12 weeks for 37.0% of T&E patients. No new safety signals were identified. CONCLUSION: IVT-AFL T&E can achieve similar functional and anatomic outcomes to fixed dosing every 8 weeks over 52 weeks in patients with nAMD who have completed ≥ 1 year of treatment, while reducing treatment burden. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02540954.

Predictors of prolonged treatment time intervals in oral cavity cancer.

OBJECTIVES: Delays in treatment time intervals have been associated with overall survival in oral cavity squamous cell carcinoma (OCSCC). The aim of this study was to identify bottlenecks leading to prolonged treatment intervals. MATERIAL AND METHODS: A retrospective analysis was conducted using a cohort of OCSCC patients who underwent surgery and adjuvant radiation therapy. The endpoints of interest were prolonged treatment intervals. Multivariable logistic regression was used to adjust for patient and tumour characteristics. RESULTS: Median diagnosis-to-treatment interval (DTI) and surgery to initiation of postoperative radiation therapy interval (S-PORT) were 39 days (IQR 30-54) and 64 days (IQR 54-66), respectively. Prolonged DTI was associated with older age, worse Charlson Comorbidity index scores and worse T stages. Patients with prolonged DTI had longer times to preoperative imaging reports (25 vs 9 days; P < 0.01). Time to preoperative pathology did not differ. Prolonged S-PORT was associated with longer times to pathology report (28 vs 18 days; P < 0.01), to maxillofacial consult (38 vs 15 days; P < 0.01) and to maxillofacial approval of radiation (50 vs 28 days; P < 0.01). In patients requiring medical oncology consults, those with prolonged S-PORT had longer waiting times until consultation (58 vs 38 days; P = 0.02). Multivariate analysis showed independent predictors of prolonged DTI: time to preoperative imaging; and prolonged S-PORT: time to pathology report, time to maxillofacial consult, and time to medical oncology consult. CONCLUSIONS: Strategies targeting these organizational bottlenecks may be effective for shortening treatment time intervals, hence representing potential opportunities for improving oncological outcomes in OCSCC patients.

Delays between Uveal Melanoma Diagnosis and Treatment Increase the Risk of Metastatic Death.

PURPOSE: To investigate if the interval between diagnosis and treatment of posterior uveal melanoma (UM) is associated with metastatic death. DESIGN: Retrospective, single-center cohort study. PARTICIPANTS: A total of 1145 patients consecutively diagnosed with posterior UM at St. Erik Eye Hospital, Stockholm, Sweden, from 2012 to 2022, with recorded dates of diagnosis and primary treatment. This cohort represents 81% of all diagnosed patients in Sweden during this period. METHODS: Data on the interval between diagnosis and treatment were collected for all patients. Its prognostic importance was examined with univariate and multivariate competing risks regressions, and cumulative incidence analyses. MAIN OUTCOME MEASURES: Incidence of metastatic death (UM mortality) for patients with prompt (< 1 month from diagnosis) versus delayed treatment (≥ 1 month) and subdistribution hazard ratios (exp(ßj)) for every additional 10-day delay in treatment. RESULTS: The mean interval between diagnosis and treatment was 34 days (SD, 56, range, 0-932). Patients treated promptly had larger tumors at diagnosis, but there were no differences in patient age, tumor distance to the optic disc, rates of ciliary body involvement (CBI) or extraocular extension (EXE), or symptom duration before diagnosis. Those who were treated more than 1 month after diagnosis had greater UM mortality in American Joint Committee on Cancer (AJCC) stage II and III. In stage I, UM mortality for delayed treatment was lower for the first 10 years, followed by a marked spike in the 11th year. In multivariate competing risks regressions of all 1145 patients with tumor diameter, thickness, CBI, and EXE as covariates, the risk for UM mortality increased with 1% for every additional 10-day delay in treatment (exp(ßj) 1.01). Among 355 patients treated with enucleation, this delay was associated with UM mortality, independent of AJCC stage, cytomorphology, and level of immunohistochemical BAP-1 expression. CONCLUSIONS: Increasing time between diagnosis and treatment of UM is associated with a higher risk of metastatic death. These results challenge a central concept in the understanding of metastatic progression and may indicate the existence of late metastatic seeding. They also underscore the importance of prompt treatment. Validation in independent cohorts is recommended. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Factors associated with diagnostic and pre-treatment intervals among breast cancer patients attending care at the Uganda Cancer Institute: A cross-sectional study.

BACKGROUND: Most breast cancer (BC) patients in Uganda are diagnosed with advanced-stage disease and experience poor outcomes. This study examined the diagnostic and pre-treatment intervals and factors associated with these intervals among BC patients attending care at the Uganda Cancer Institute (UCI). METHODS: This was a cross-sectional, facility-based study. Data were collected using structured questionnaire administered by trained research assistants and analyzed using STATA version 14.0. Modified Poisson regressions models were used to determine the strength of associations between independent variables and diagnostic and pre-treatment intervals. RESULTS: The mean age (±SD) of the 401 participants was 47.1 ± 11.7 years. Four in 10 participants had stage III (41.9%; n = 168) and over a third (34.7%; n = 140) stage IV cancers. The median interval from first consultation to diagnosis, i.e. diagnostic interval (DI) was 5.6 months (IQR: 1.5-17.0), while the median interval from histological diagnosis to start of chemotherapy, i.e. pre-treatment interval (PTI) was 1.7 months (IQR: 0.7-4.5). Majority (85%, n = 341) of participants were diagnosed at ≥3 months from first consultation with clinicians. Participants with tertiary education and those who lived within 100-199 km from the UCI were about four times and twice more likely to be diagnosed early (DI <3 months from first consultation) ([aPR = 3.88; 95% CI: 1.15-13.0] and [aPR = 2.19; 95% CI: 1.06-4.55]), respectively. About half (48.3%; n = 176) of participants started chemotherapy within 1 month of cancer diagnosis. Patients who lived more than 300 km from the UCI were less likely to start chemotherapy within 1 month of histology diagnosis of cancer. [Correction added on October 17, 2023 after first online publication. The term ', i.e.' has been included in the results section in this version.] CONCLUSION: Majority of breast cancer patients are diagnosed late and in advanced stages. There is need to promote all efforts toward timely diagnosis when cancers are still in early stages by identifying factors responsible for prolonged diagnostic intervals among breast cancer patients.

Switching to Dupilumab from Other Biologics without a Treatment Interval in Patients with Severe Asthma: A Multi-Center Retrospective Study.

BACKGROUND: Dupilumab is a fully humanized monoclonal antibody that blocks interleukin-4 and interleukin-13 signals. Several large clinical trials have demonstrated the efficacy of dupilumab in patients with severe asthma. However, few studies have examined a switch to dupilumab from other biologics. METHODS: This retrospective, multi-center observational study was conducted by the Okayama Respiratory Disease Study Group. Consecutive patients with severe asthma who were switched to dupilumab from other biologics without a treatment interval between May 2019 and September 2021 were enrolled. Patients with a treatment interval of more than twice the standard dosing interval for the previous biologic prior to dupilumab administration were excluded. RESULTS: The median patient age of the 27 patients enrolled in this study was 57 years (IQR, 45-68 years). Eosinophilic chronic rhinosinusitis (ECRS)/chronic rhinosinusitis with nasal polyp (CRSwNP) was confirmed in 23 patients. Previous biologics consisted of omalizumab (n = 3), mepolizumab (n = 3), and benralizumab (n = 21). Dupilumab significantly improved FEV1 (median improvement: +145 mL) and the asthma control test score (median improvement: +2). The overall response rate in patients receiving dupilumab for asthma as determined using the Global Evaluations of Treatment Effectiveness (GETE) was 77.8%. There were no significant differences in the baseline characteristics of the GETE-improved group vs. the non-GETE-improved group. ECRS/CRSwNP improved in 20 of the 23 patients (87.0%). Overall, 8 of the 27 patients (29.6%) developed transient hypereosinophilia (>1500/µL), but all were asymptomatic and able to continue dupilumab therapy. CONCLUSIONS: Dupilumab was highly effective for the treatment of severe asthma and ECRS/CRSwNP, even in patients switched from other biologics without a treatment interval.

The impact of time to surgery on oncological outcomes in stage I-III dMMR colon cancer - A nationwide cohort study.

INTRODUCTION: One of the considerations when investigating neoadjuvant interventions is the prolonging of time from diagnosis to curative surgery (i.e. the treatment interval [TI]). The aim of this study was to investigate the association between the length of TI and overall survival and disease-free survival in patients with deficient mismatch repair (dMMR) colon cancer. MATERIALS AND METHODS: This retrospective propensity score-adjusted study included all patients of ≥18 years of age undergoing elective curative surgery for stage I-III, dMMR colon cancer. Data were extracted from four Danish patient databases. Outcomes were investigated in groups with TIs of ≤14 days versus >14 days. Propensity scores were computed using all demographics, diagnoses and measurements. Matching was done in a 1:1 ratio. RESULTS: A total of 4130 patients were included in the study with a mean age of 73.8 years and a median follow-up time of 43.9 months. After matching, 2794 patients were included in the analysis of overall survival. No significant difference in overall survival was seen between patients with TIs of ≤14 days versus >14 days (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.81-1.17; p = 0.78). In the analysis of disease-free survival, 1798 patients were included after matching. This showed no significant difference between patients with TIs of ≤14 days versus >14 days (HR, 0.85; 95% CI, 0.69-1.06; p = 0.14). CONCLUSION: No associations were found between TI and overall survival and disease-free survival in patients with stage I-III, dMMR colon cancer undergoing elective curative surgery.

Time interval between diagnosis to treatment of breast cancer and the impact of health insurance coverage: a sub analysis of the AMAZONA III Study (GBECAM 0115).

PURPOSE: Breast cancer (BC) is the most common type of cancer among women in Brazil. Evidence shows that delayed treatment onset is associated with increased mortality. This study aimed to evaluate median days between diagnosis and treatment and factors associated with delayed start of treatment (> 60 days after diagnosis): stage, treatment received, subtype, epidemiological characteristics, and type of healthcare coverage. METHODS: This analysis included 1709 stage I-III BC patients from AMAZONA III, a prospective, observational study, diagnosed from January 2016 to March 2018 in 22 centers in Brazil. RESULTS: The median number of days from diagnosis to beginning of first oncologic treatment was 46 days (IQR 28-75) overall, 43 days (IQR 25-75) for stage I disease, 49 days (IQR 28-81) for stage II, and 44 days (IQR 30-68) for stage III, (p = 0.1180). According to first treatment received, diagnosis-to-treatment interval was 43 days (IQR 29-65) for neoadjuvant chemotherapy and 48 days (IQR 26-81) for surgery. Diagnosis-to-treatment interval was higher in women treated in the public system versus the private system (56 vs. 34 days, p < 0.0001). Patients in the public system had an increased odds of delayed treatment initiation (OR 4.74 95% CI 3.09-7.26, p < .0001). The longer interval from diagnosis to treatment in the public system was independent of clinical stage, type of treatment (systemic vs surgery first), subtype and region of the country. CONCLUSION: By characterizing the delays in care delivery, our study will aid stakeholders to better design interventions and allocate resource to improve timely treatment for breast cancer in Brazil. CLINICALTRIALS: gov Identifier: NCT02663973, registered on January, 26th, 2016.

Diagnosis and Management of Classical Hodgkin Lymphoma During the COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has brought life to a standstill globally. Intermittent quarantines were applied to control the pandemic and reduce contamination. During the pandemic, patients with hematological malignancies were among the most vulnerable population. Our aim was to compare in terms of demographic data, disease-related factors, symptom-to-diagnosis interval, diagnosis-to-treatment interval , and interim and end-of-treatment response in classical Hodgkin lymphoma patients diagnosed during the pandemic and in the pre-pandemic periods. A total of 90 patients were included, of which 65 and 25 were diagnosed in the 2 years before the pandemic and the 12-month period during the pandemic, respectively. Demographic features were comparable in both groups. Although the percentage of patients with advanced-stage disease was higher during the pandemic (64% vs 53.8%), this difference did not reach statistical significance (P = 0.384). The median symptom-to-diagnosis interval was significantly longer during the pandemic than was observed within the pre-pandemic era (16 weeks vs 8 weeks, P = 0.042). The median diagnosis-to-treatment intervals was similar in both groups (13 days vs 15 days, P = 0.253). In the pre-pandemic and pandemic periods, 85.2% and 72.7% of the patients had complete response at end-of-treatment evaluation, respectively (P = 0.208). We found that symptom-to-diagnosis interval was significantly prolonged during the pandemic. Higher percentage of patients with advanced-stage disease during the pandemic might also be due to this delay, nevertheless, this difference did not reach to a significant difference regarding treatment response in both groups.

YOSEMITE and RHINE: Phase 3 Randomized Clinical Trials of Faricimab for Diabetic Macular Edema: Study Design and Rationale.

Purpose: Faricimab is a novel anti-angiopoietin-2 and anti-vascular endothelial growth factor (VEGF) bispecific antibody with high affinities and specificities for both VEGF and angiopoietin-2. It is postulated that targeting angiogenic factors and inflammatory pathways in addition to the VEGF pathway will increase treatment durability and improve outcomes. The phase 3 YOSEMITE (ClinicalTrials.gov identifier, NCT03622580) and RHINE (ClinicalTrials.gov identifier, NCT03622593) trials are designed to assess efficacy, safety, and durability of faricimab compared with aflibercept in patients with diabetic macular edema (DME). The trials evaluate a personalized treatment interval (PTI) approach to address heterogeneity in treatment response among patients with DME. Design: Two identically designed, global, double-masked, randomized, controlled phase 3 trials (YOSEMITE and RHINE). Participants: Adults with center-involving DME secondary to type 1 or 2 diabetes mellitus. Methods: These studies were designed to evaluate 3 treatment groups: faricimab 6.0 mg dosed either at fixed dosing every 8 weeks after initial treatment with 6 intravitreal doses at 4-week intervals, or faricimab 6.0 mg dosed according to PTI after initial treatment with 4 every-4-week doses, compared with aflibercept 2.0 mg dosed every 8 weeks after 5 initial every-4-week doses. The primary end point of the studies was change from baseline in best-corrected visual acuity at 1 year, averaged over weeks 48, 52, and 56. Secondary end points included anatomic, durability, and patient-reported outcomes. Safety outcomes included incidence and severity of ocular and nonocular adverse events. The PTI is a protocol-defined flexible regimen based on the treat-and-extend concept, which allowed up to every-16-week adjustable dosing based on objective and standardized criteria. The PTI design aimed to maximize therapeutic results while minimizing treatment burden. Main Outcome Measures: We describe the rationale for the study design and the novel PTI (up to every-16-week adjustable dosing) approach for treatment with faricimab. Results: YOSEMITE and RHINE enrolled 940 and 951 patients, respectively. Results from each study will be reported separately. Conclusions: YOSEMITE and RHINE were the first registrational trials in retinal disease to incorporate an objective PTI regimen, allowing for up to every-16-week adjustable dosing with a dual angiopoietin-2 and VEGF-A inhibitor, faricimab 6.0 mg, for treatment of DME.

Time to Surgery for Patients with Esophageal Cancer Undergoing Trimodal Therapy in Ontario: A Population-Based Cross-Sectional Study.

Patients with resectable esophageal cancer are recommended to undergo chemoradiotherapy before esophagectomy. A longer time to surgery (TTS) and/or time to consultation (TTC) may be associated with inferior cancer-related outcomes and heightened anxiety. Thoracic cancer surgery centers (TCSCs) oversee esophageal cancer management, but differences in TTC/TTS between centers have not yet been examined. This Ontario population-level study used linked administrative healthcare databases to investigate patients with esophageal cancer between 2013-2018, who underwent neoadjuvant chemoradiotherapy and then surgery. TTC and TTS were time from diagnosis to the first surgical consultation and then to surgery, respectively. Patients were assigned a TCSC based on the location of the surgery. Patient, disease, and diagnosing physician characteristics were investigated. Quantile regression was used to model TTS/TTC at the 50th and 90th percentiles and identify associated factors. The median TTS and TTC were 130 and 29 days, respectively. The adjusted differences between the TCSCs with the longest and shortest median TTS and TTC were 32 and 18 days, respectively. Increasing age was associated with a 16-day longer median TTS. Increasing material deprivation was associated with a 6-day longer median TTC. Significant geographic variability exists in TTS and TTC. Therefore, the investigation of TCSC characteristics is warranted. Shortening wait times may reduce patient anxiety and improve the control of esophageal cancer.

Efficacy and Safety of Intravitreal Aflibercept Treat-and-Extend Regimens in the ALTAIR Study: 96-Week Outcomes in the Polypoidal Choroidal Vasculopathy Subgroup.

INTRODUCTION: To explore the efficacy and safety of intravitreal aflibercept (IVT-AFL) proactive, individualized treat-and-extend (T&E) regimens in exudative age-related macular degeneration (AMD) in the subgroup of patients with polypoidal choroidal vasculopathy (PCV) enrolled in the ALTAIR study. METHODS: This was a PCV subgroup analysis of ALTAIR, a 96-week, randomized, open-label, phase 4 study in treatment-naïve patients with exudative AMD in Japan. Following three initial monthly doses, patients received IVT-AFL at week 16 and were randomized 1:1 to T&E regimens with either 2-week (IVT-AFL-2W) or 4-week (IVT-AFL-4W) adjustments. The primary endpoint of ALTAIR was the mean change in best-corrected visual acuity (BCVA) from baseline to week 52. Endpoints were assessed at weeks 52 and 96. Safety analyses were conducted. RESULTS: A total of 90 patients with PCV were included within the full analysis set. From baseline to week 52, mean [standard deviation (SD)] change in BCVA was + 7.5 (14.7) letters and + 8.2 (11.6) letters in the IVT-AFL-2W and IVT-AFL-4W groups, respectively. From baseline to week 96, 91.3% and 90.9% of patients maintained vision in the IVT-AFL-2W and IVT-AFL-4W groups, respectively. From baseline to week 52, mean (SD) change in central retinal thickness was - 153 (177) µm and -112 (122) µm in the IVT-AFL-2W and IVT-AFL-4W groups, respectively. Overall, 51.1% of patients (IVT-AFL-2W, 43.5%; IVT-AFL-4W, 59.1%) achieved a treatment interval of 16 weeks between weeks 16 and 96. The safety profile of IVT-AFL was consistent with previous studies. CONCLUSION: In treatment-naïve patients with PCV, IVT-AFL administered using two different T&E regimens improved and maintained functional and anatomic outcomes over 96 weeks while minimizing treatment burden. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02305238.

Time to treatment of esophageal cancer in Ontario: A population-level cross-sectional study.

Objective: Timely cancer treatment improves survival and anxiety for some sites. Patients with esophageal cancer require specific workup before treatment, which can prolong the time from diagnosis to treatment (treatment interval [TI]). The geographical variation of this interval remains uninvestigated in patients with esophageal cancer. Methods: This retrospective population-level study conducted in Ontario used linked administrative health care databases. Patients treated for esophageal cancer between 2013 and 2018 were included. The TI was time from diagnosis to treatment. Patients were assigned a geographical Local Health Integration Network on the basis of postal code. Covariates included patient, disease, and diagnosing physician characteristics. Quantile regression modeled TI length at the 50th and 90th percentile and identified associated factors. Results: Of 7509 patients, 78% were male and most were aged between 60 and 69 years. The 50th and 90th percentile TI was 36 (interquartile range, 22-55) and 77 days, respectively. The difference between the Local Health Integration Network with the longest and shortest TI at the 50th and 90th percentile was 18 and 25 days, respectively. Older age (P < .0001), greater comorbidity (P = .0005), greater material deprivation (P = .001), rurality (P = .03), histology (P = .02), and treatment group (P < .0001) were associated with a longer median TI. Older age (P = .03), greater comorbidity (P = .003), greater material deprivation (P = .005), rurality (P = .04), and treatment group (P < .0001) were associated with a longer 90th percentile TI. Conclusions: Geographic variability of time to treatment exists across Ontario. Investigation of facility-level differences is warranted. Patient and disease factors are associated with longer wait times. These results might inform future health care policy and resource allocation.

Oligometastatic adenoid cystic carcinoma: Correlating tumor burden and time to treatment with outcomes.

BACKGROUND: There is limited information on the management and outcomes of oligometastases (OM) in adenoid cystic carcinoma (ACC). METHODS: Retrospective study of 42 patients with metastatic ACC of the head and neck. Imaging studies were analyzed to identify patients with OM (1-5 lesions) at any point during follow-up. RESULTS: There was radiographic evidence of OM in 33/42 (79%) patients. Eighteen patients had OM when treated for metastases, with median overall survival (OS) of 36.0 versus 9.2 years for patients with polymetastases (6+ lesions, HR 0.38, 95%CI 0.14-0.89). Earlier locally ablative treatment, but not systemic treatment, of patients with OM predicted improved survival 3 years after metastasis (HR 0.15, 95%CI 0.02-0.63) and postponed systemic treatment by 80 more months (HR 0.22, 95%CI 0.07-0.71). CONCLUSIONS: There is a considerable population of ACC patients with detectable oligometastases, and early locally ablative treatment of oligometastases may be associated with improved outcomes.

Health system factors that influence diagnostic and treatment intervals in women with breast cancer in sub-Saharan Africa: a systematic review.

BACKGROUND: Breast cancer patients in sub-Saharan Africa experience long time intervals between their first presentation to a health care facility and the start of cancer treatment. The role of the health system in the increasing treatment time intervals has not been widely investigated. This review aimed to identify existing information on health system factors that influence diagnostic and treatment intervals in women with breast cancer in sub-Saharan Africa to contribute to the reorientation of health policies in the region. METHODS: PubMed, ScienceDirect, African Journals Online, Mendeley, ResearchGate and Google Scholar were searched to identify relevant studies published between 2010 and July 2020. We performed a qualitative synthesis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Related health system factors were extracted and classified according to the World Health Organization's six health system building blocks. The quality of qualitative and quantitative studies was assessed by using the Critical Appraisal Skills Program Quality-Assessment Tool and the National Institute of Health Quality Assessment Tool, respectively. In addition, we used the Confidence in the Evidence from Reviews of Qualitative Research tool to assess the evidence for each qualitative finding. RESULTS: From 14,184 identified studies, this systematic review included 28 articles. We identified a total of 36 barriers and 8 facilitators that may influence diagnostic and treatment intervals in women with breast cancer. The principal health system factors identified were mainly related to human resources and service delivery, particularly difficulty accessing health care, diagnostic errors, poor management, and treatment cost. CONCLUSION: The present review shows that diagnostic and treatment intervals among women with breast cancer in sub-Saharan Africa are influenced by many related health system factors. Policy makers in sub-Saharan Africa need to tackle the financial accessibility to breast cancer treatment by adequate universal health coverage policies and reinforce the clinical competencies for health workers to ensure timely diagnosis and appropriate care for women with breast cancer in this region.

Neovascular age-related macular degeneration at treatment intervals of 14 weeks or greater.

BACKGROUND: We assessed the proportion of eyes with neovascular age-related macular degeneration (nAMD) in routine clinical practice that reach ≥14 week treatment intervals and their outcomes. METHOD: We analysed data from the Fight Retinal Blindness! (FRB!) Project database, a prospectively designed registry of 'real-world' outcomes. Treatment-naive eyes starting vascular endothelial growth factor (VEGF) inhibitors for nAMD from 1st January 2006 were included. Eyes were defined to have reached the ≥14 week treatment interval if they received ≥2 consecutive injections at treatment intervals of ≥14 week but not exceeding 26 weeks. Outcomes were reported in a subgroup of eyes that had 12 months of follow-up from reaching this interval. RESULTS: Of the 3907 treatment-naïve eyes that started treatment during the identified periods on a treat-and-extend regimen and received at least 8 injections over the first 2 years, 402 (10%) eyes received at least 2 consecutive injections at an interval of ≥14 week during their follow-up. Fifty-two percent of these eyes maintained vision to 12 months, however only 40% stayed at this interval and 25% of the lesions reactivated. CONCLUSION: We found that only 10% of eyes with nAMD were extended beyond a 13-week injection interval and that over half had returned to a shorter interval by 12 months. Eyes that stayed at this extended treatment interval maintained stable vision. More data on the outcomes of eyes treated with intervals longer than 3 months are required to establish whether emerging VEGF inhibitors provide a more sustained effect than the currently available drugs.